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Coronavirus Disease 2019 (COVID-19) is a severe respiratory disease that results from infection with a new coronavirus (SARSCOV- 2) [1]. One of the most critical issues related to the COVID-19 is the high rate of spread, millions of people have been infected around the world, and hundreds of thousands of deaths till now have been recorded [1]. Patients suffering from different symptoms like fever, dry cough, and fatigue are usually mild in about 80% of cases. Still, the more severe cases may develop respiratory distress or respiratory failure, hence the increased need for intensive care unit (ICU) services [1].

The severity of the disease is related to the age and comorbidities of the infected person; elderly persons are affected more severely with a need for ICU services [2]. The severity of symptoms is also related to its duration, where for mild cases, symptoms may last for two weeks, while for severe cases, it ranges from 3 to 6 weeks [3]. Direct contacts to confirmed cases are the disease’s primary way of spreading because the SARS-COV-2 is transmitted through exhaled air and aerosols [4]. Diagnosis of COVID-19 is conducted using Reverse Transcriptase Polymer Chain Reaction (RT-PCR), Computed Tomography (CT) scan, and blood tests [5]. Supportive treatment is the primary choice for mild cases, including antibiotics, vitamins, trace elements, and antipyretics [6]. At the same time, oxygen therapy with or without mechanical ventilation is introduced and individualized according to each case [6].

Many drugs have been included in clinical trials to act as antiviral agents to the coronavirus disease. Still, no precise results indicate the confirmed effect for any investigated drugs [7-9]. In addition to symptomatic therapy, corticosteroids as an anti-inflammatory agent have been found to play a vital role in the management of severe cases of the COVID-19 [10].

Thousands of infected patients have recovered from the disease. This recovery is confirmed by conducting another RT-PCR test or by the absence of the symptoms of the disease for several days. However, few documented studies in Uganda provide information on the clinical characterization of COVID-19 cases, treatment outcomes, and factors associated with clinical presentations and treatment outcomes.

The objective of this study was to describe the characteristics of the COVID-19 patients treated at the Gulu Regional Referral Hospital and determine factors associated with the COVID-19 manifestations, socio-demographic characteristics, and treatment outcomes.

Study site

This study was conducted in Gulu Regional Referral Hospital in Northern Uganda, covering admissions of COVID-19 patients from March 2020 to October 2021. Gulu Hospital is a regional referral centre for patients from Northern Uganda. However, it receives patients from neighbouring countries, for example, South Sudan and the Democratic Republic of Congo (DR Congo). It is also a teaching hospital for Gulu University Medical School and many other health training institutions in the region. It is a 394-bed capacity hospital with outpatient and inpatients services estimated at 120,000 patients every year. The Hospital has specialized units such as internal medicine, surgery, paediatrics, reproductive health, TB, HIV, cardiac, chest, dental, dermatology, sickle cell disease, diabetes, hypertension, ear, nose and throat, nutrition, accident and emergency, laboratory, ophthalmology, mental health, and orthopaedic clinics that consultants from Gulu Regional Referral Hospital and Gulu University manage.

Gulu Regional Referral Hospital was designated by the Ugandan Ministry of Health as a treatment centre for COVID-19 patients in March 2020 when COVID-19 was declared a pandemic. As a result, a particular treatment unit for the management of COVID-19 (Gulu CTU) was established with a fully-fledged high dependency unit (HDU), with oxygen supply and staff to manage the department. The team leader for the Gulu CTU is a consultant physician who cares for all the COVID-19 patients admitted to the unit. In addition, the Ugandan Ministry of Health and WHO health experts provided additional support for managing the COVID-19 patients at the centre using standard protocols developed and practiced in Uganda.

Study design

A retrospective data review and abstraction of all COVID-19 hospital admissions registered in the Gulu Health Management Information System (HMIS) database and other tools were conducted. The period of the review was March 2020 to October 2021. Established by the Ugandan Ministry of Health, HMIS has been the primary source of information on COVID-19 hospital admissions and deaths. COVID-19 notification is compulsory in Uganda, and the emergency operation centre at the Uganda National Public Health Institute receives reports on patients admitted to both public and private hospitals with COVID-19.

Sources of data

For the period of this study, COVID-19 patients admitted to Gulu Regional Referral Hospital with COVID-19 were estimated at nine hundred and forty-four (944). We included every patient registered in the HMIS database. Information on individual's socio-demographic characteristics, self-reported symptoms, signs, comorbidities, COVID-19 Treatment Unit (CTU) admissions, ICU admissions, and ventilatory support, dates of symptoms’ onset, dates of hospital admissions, dates of discharges/ releases, duration of the hospital stay, the reported circumstances of contracting the coronavirus, the vaccination status and hospital outcomes (deaths, referrals, and releases/discharges) were documented. HMIS data were accessed, which were already de-identified and publicly available documents. Following ethically agreed principles on open data access, this review did not require stringent ethical approval in Uganda as we mainly worked on records with no identifiers included. However, we obtained ethical and administrative licenses from the Gulu Regional Referral Hospital Institution and Ethics Review Committee to access the archived Gulu Hospital data on COVID-19 patients.

Selection criteria

Inclusion criteria:

• Confirmed cases of COVID-19 with RT-PCR.

• Records of patients 12 years and above.

• Completed information on the chart and other medical tools.

• Admission records.

Exclusion criteria:

We excluded:

• Incomplete records.

• Participants below 12 years.

Selection of records: The medical records for the COVID-19 patients in Gulu Regional Referral Hospital archives were accessed. The selection of the COVID-19 patients' files was conducted consecutively and reviewed by the research team. The selection criteria were applied to each admission file (a total of nine hundred and forty-four files); seven (7) were excluded due to lack of RT-PCR results; thirteen (13) patients were less than twelve years; fifty-six (56) patients had incomplete files; ninety-six (96) patients appeared in HMIS database without admission files; one hundred and five (108) patients had insufficient medical history on the file, and finally a total of six hundred and sixty-four (664) files were included in the participating medical records for this research.

Sample size: We determined the sample size for the study population using the selection criteria on the medical records. Six hundred and sixtyfour (664) records were included as the sampled population.

Training of research assistants: To obtain excellent and clean information from these COVID-19 patients' medical files, the research team trained the research assistants who were four in number (two medical officers, one clinical officer, and one nurse) on how to use the selection criteria, accurately record data from the admission forms and exclude forms that were considered incomplete. The research assistants were trained on infection, prevention, and control of COVID-19 and were required to use facemasks, eye shields, and sanitizers during and after reviewing documents. The corresponding author supervised the data collection exercise from the beginning to the end, ensuring that he checked every file to confirm the completeness of the data collected.

Procedures for data collection: Consecutively registered COVID-19 patients treated at Gulu Regional Referral Hospital with a positive quantitative RT-PCR test result for SARS-CoV-2 admitted to Gulu Hospital were recruited. SARS-CoV-2 diagnostic tests followed National and International standards. They were conducted in certified laboratories of Gulu Regional Referral Hospital and Uganda Virus Research Institute (UVRI) as the Ugandan Ministry of Health protocols required.

Variables for the study: The dependent variables for this study were treatment outcomes (alive or dead). The independent variables were the socio-demographic characteristics of the COVID-19 patients (age, sex, occupation, religion, tribe, districts, and level of education), comorbidities and treatments used, oxygen saturation at admission, date of discharge from the hospital, duration of hospital stay, disease severity, and others), clinical presentations (signs and symptoms), vaccination status, residences, and circumstances under which COVID-19 patients contracted the coronavirus.

Data analysis: The analysis period was from the epidemiological week (starting month and date of March 2020) to the epidemiological week (until month and date of October 2021). The analysis was pre-specified and defined before reading the medical data in the Gulu Regional Referral Hospital records. The sample size was all patients (aged ≥ 12 years) with confirmed COVID-19 diagnosis who were admitted to the Gulu Hospital and registered in the database between the epidemiological weeks of March 2020 and October 2021.

Means, standard deviations, bar graphs, histograms, frequencies, and percentages were used to summarize continuous variables, while frequencies and proportions were calculated for categorical variables. Ageadjusted and sex-adjusted rates for each district by the direct method using the estimated Ugandan population for 2020 as a reference were calculated.

We used the Chi-Square tests at bivariate analysis to observe associations between independent and dependent variables at 95% confidence Intervals. Factors with p-values less or equal to 0.2 were entered into a multivariable regression analysis to determine factors associated with COVID-19 patients treated at GRRH. However, the Gulu Hospital HMIS data contained much-missing information for some variables, such as reported symptoms, medicines used, and comorbidities. Therefore, we used additional GRRH records to fill in the missing data. Also, in the post hoc analysis, we evaluated the missing data pattern and conducted a sensitivity analysis via multiple imputations by chained equations, generating 30 imputed datasets. SPSS version 25.0 was used for data analysis, and various imputations were performed utilizing the STROBE guideline recommendations. In addition, Adjusted Odds Ratios (AOR) for independent variables were calculated for the COVID-19 patients treated at the Gulu Regional Referral Hospital from March 2020 to October 2021.

Ethical considerations: This retrospective data review of COVID-19 patients' medical files at the Gulu Regional Referral Hospital was approved by the Gulu Regional Hospital Institutional, Ethics, and Review Committee.

This study abstracted six hundred and sixty-four (664) medical records of COVID-19 patients treated at the Gulu Regional Referral Hospital from March 2020 to October 2021. Only medical records of COVID-19 patients that met the inclusion criteria for the study were included. Most COVID-19 patients treated at the GRRH recovered from the disease with a recovery rate of 632(95.2%) and a mortality rate of 32(4.8%). In addition, most COVID-19 patients treated at the Hospital were unvaccinated 661(99.5%) for COVID-19.

In Figure 1, there were three waves of COVID-19 in Gulu, Northern Uganda, and these were May and September in 2020. In addition, there was a small observable wave in July 2021.

In Figure 2, COVID-19 discharges from the CTU of Gulu Regional Referral Hospital mirrored the admission pattern where June, October of 2020, and July 2021 registered the most releases from the CTU.

Figure 3 shows the peak duration of Hospital stays (days) among COVID-19 patients treated at GRRH as 16 days.

In Table 1, most COVID-19 patients treated at the Gulu Regional Referral Hospital from March 2020 to October 2021 were males 443(66.7%), age group 30-39 years old 204(30.7%); Certificate holders of education 152(32.6%), Acholi 386(59.2%), Catholics 95(46.3%), Civil Servants 97(19.0%) and from Gulu District 226(34.0%).

Table 1: Socio-demographic characteristics of COVID-19 patients treated at Gulu Regional Hospital.

Tables 2 and 3 shows drugs used for the treatment of COVID-19 at GRRH: antibiotics 662(99.7%), Vitamin C 564(84.9%), steroids 73(11.0%), Vitamin D 24(3.6%), Ivermectin 7(1.1%), and Aspirin 2(0.3%) in the descending order.

Table 2: Symptoms and comorbidities among COVID-19 patients treated at Gulu Regional Hospital.

Table 3: Drugs used for the treatment of COVID-19 patients at Gulu Regional Referral Hospital.

In Table 4, complications observed in COVID-19 patients treated at GRRH were pneumonia 60(9.0%), chronic fatigue 49(7.4%), acute respiratory distress syndrome (ARDS) 37(5.6%), acute respiratory failure 30(4.5%); depression 20(3.0%), systemic infections 19(2.9%), nightmares 15(2.3%) and septic shock 8(1.2%).

Table 4: Complications in the COVID-19 patients treated at the Gulu Regional Hospital.

In Tables 5 and 6, most COVID-19 patients treated in GRRH were in the hospital for one week 216(44.9%); oxygen saturation (SpO₂) at admission was >96 394(81.9%); did not use Aspirin 479(99.6%), steroids 415 (86.3%), Garlic 480 (99.8%), Lemon 478(99.4%), Ivermectin 474(98.4%), Vitamin D 458(95.2%), and steaming 479 (99.6%) but used Antibiotics 480(99.8%) for treatment.

Table 5: Cross tabulations between variables in COVID-19 patients treated at Gulu Regional Referral Hospital.

Table 6: Characteristics of COVID-19 patients treated at Gulu Regional Referral Hospital.

In Table 7, factors associated with COVID-19 patients treated at Gulu Regional Referral Hospital were Diabetes mellitus χ²=1.156; df=1; p<0.0000; other cardiovascular diseases (CVDs) χ²=34.819; df=1; p<0.0000; hypertension χ²=10.807; df=1; p=0.0010; HIV and AIDs χ²=6.488; df=1; p=0.011; treatment with steroids χ2=157.639; df=1; p<0.0000;Vitamin D χ²=113.521; df=1; p<0.0000; vitamin C χ²=56.548; df=1; p<0.0000; Ivermectin χ²=82.886; df=1; 0.0000; Oxygen saturation(SpO₂) 80-96 χ²=29.357; df=1; p<0.0000; Oxygen saturation (<96) χ²=42.962; df=1; p<0.0000; duration of hospital stay (less than one week) χ²=57.690; df=1; p<0.0000; duration of hospital stay (two weeks) χ²=6.569; df=1; p=0.010 and duration of hospital stay (six weeks) χ²=4.180; df=1; 0.041.

Table 7: Factors associated with COVID-19 patients treated at Gulu Regional Referral Hospital CTU.

In Table 8, the Adjusted Odds Ratios (AOR) for factors associated with COVID-19 patients treated at Gulu Regional Referral Hospital. Treatment with steroids AOR=138.835 at 95% CI: 12.258-1572.50; p<0.000 and Vitamin D AOR=0.016 at 95% CI:1.902-520.98; p=0.016.

Table 8: Multivariable logistic regression showing treatment, Oxygen saturation (SpO₂), and duration of hospital stay for COVID-19 patients treated at GRRH.

The most significant findings were the three waves of COVID-19 in Gulu in Northern Uganda, and these were in May and September of 2020 and July of 2021 (Figures 1-3). The third wave of COVID-19 in 2021 was less pronounced (Figures 1-3). This finding contrasts with the official Ugandan Ministry of Health position on the number of COVID-19 waves Uganda has gone through since the pandemic began in March 2020. The Ugandan Ministry of Health specified two waves of the COVID-19: one in 2020 and another in June 2021. This Ugandan Ministry of Health report is not surprising as regional waves of COVID-19 have been reported in many studies [11-14]. This finding has implications on how Uganda could respond to the COVID-19 waves as the regional approach to managing and controlling the pandemic has become eminent. The regional occurrence of the COVID-19 wave has advantages in that the Ugandan Ministry of Health could use this information to harness support and allocate resources to effectively manage and control the pandemic at the regional level in different parts of the Country. This may include mass mobilization and sensitization of the population at a regional level to embrace mass vaccination with the COVID-19 vaccines now that they are available in the Country. It is expected that this approach could limit the spreading of COVID-19 country-wide and reduce the morbidity and mortality of the coronavirus in Northern Uganda.

Figure 1: The pattern of COVID-19 admissions to the Gulu Treatment Unit (CTU).

Figure 2: The pattern of discharges of COVID-19 patients treated at the CTU of Gulu Regional Referral Hospital.

Figure 3: Duration of hospital stays (days) of COVID-19 patients treated at Gulu Regional Hospital.

Socio-demographic characteristics of the COVID-19 patients

Findings from this study show that most COVID-19 patients treated at the Gulu Regional Referral Hospital were males, 30-39 years-old, Acholi, Catholics with certificates as the highest level of education, civil servants, and from Gulu District (Table 1). These socio-demographic characteristics are comparable to previous studies conducted in Northern Uganda, where the most affected people were males and certificates at their highest level of education attained (Table 1). What is different in this study population is that the most affected age group is a decade older (Table 1) compared to previous studies in Northern Uganda, where most participants were 20–29-years-old [15,16].

The age factor could be explained by the susceptibility pattern of the COVID-19 among the older population of Northern Uganda and elsewhere. The aging population appears more vulnerable and susceptible. The overall reasons for the susceptibility in the older people in Northern Uganda may not be known for now but perhaps attributable to lifestyles, exposure to multiple risk factors, comorbidities, and immunity problems of the more aging population. As shown in Table 1, the younger age groups were least affected as per the GRRH COVID-19 treatment centre's admission details. However, it could also mean that many of the younger age groups got affected but remained asymptomatic, did not test for COVID-19, did not develop severe disease, and did not get hospitalized with the coronavirus.

Findings from this current study show that nearly one-fourth of the COVID-19 patients treated were asymptomatic, and less than 10% of the patients were below 20 years of age (Table 3). These authors argue that this information was not wholly new. Similar findings in many studies conducted elsewhere in the world show that younger persons were least susceptible to severe COVID-19 and chances of hospitalization [13,14,17].

Factors associated with the COVID-19 patients treated at the Gulu Regional Referral Hospital

This report shows that most COVID-19 patients treated for severe COVID-19 and died at the GRRH had comorbidities, for example, Diabetes mellitus, cardiovascular diseases (CVDs) including (Stroke, valvular heart diseases, dysrhythmias, heart failure, and cardiac septal defects), hypertension, and symptomatic cases (Tables 2 and 3). Many studies have observed similar findings, particularly those with comorbidities [2,17,18]. This finding implies that the Ugandan Ministry of Health could adopt the "Enhanced shielding" approach, where persons with comorbidities and the elderly are shielded from the general population to protect them from contracting the COVID-19 virus [12,19]. These suggestions have implications on the approach the Ugandan health systems could adopt to control the spreading of COVID-19 among the elderly and those with comorbid conditions. The rural structure and relationship between the elderly and younger generation need thorough analysis as the elderly in the rural communities live with and together with young people who provide support and protection to the elderly. The practicality of this approach needs thorough thinking as this new approach may disrupt traditional ways of how people in the African rural communities live. These authors argue that with the lockdown, the economy, and health systems collapsing in many African countries, it is high time government planners came with solutions that allow the economy to be opened but ensure a reduced incidence and prevalence of COVID-19 in communities. One of the recommended approaches was to practice the enhanced shielding approach, which is more favourable to a country's social and economic systems. In addition, there is a need to sensitize and mobilize the population to embrace mass COVID-19 vaccination as vaccines are now available in the country to reduce the incidence of severe COVID-19, which require hospitalization.

Treatment and complications observed among COVID-19 patients in Gulu Regional Referral Hospital

Findings from this study show that most COVID-19 patients were treated with antibiotics, vitamin C, steroids, Ivermectin, and vitamin D (Tables 3-7) and the outcomes of the treatment have been encouraging as shown by the very high recovery rate at 95.2% and a statistically significant association with steroid and Vitamin D treatment (Table 8).

In the same study, the most typical complications observed among the COVID-19 patients were pneumonia, acute respiratory distress syndrome (ARDS), systemic infections, septic shock, chronic fatigue, depression, and nightmares (Table 4). These authors argue that there were justified reasons for using antibiotics in treating COVID-19 patients at Gulu Hospital, as many cases developed complications treated with antibiotics.

In addition, the role played by the other drugs in the management of COVID-19 was suggested by scholars and academicians across the world and particularly their use as immune system modulators [17]. To come up with a conclusive decision on the beneficial effects of the two drugs for managing COVID-19 patients at GRRH, formal Randomized Controlled Trials will be required.

On the mental health complications observed among the COVID-19 patients treated at the Gulu Regional Referral Hospital, authors recommend comprehensive mental health support for COVID-19 patients and the follow-up after recovery. Effective management of mental health conditions such as depression relieves the ever-increasing sense of depression and isolation experienced by the COVID-19 patients. If the numbers of mental health cases become widespread, a grass-root approach using trained village health teams (VHTs) would be the recommended approach for handling the problem. Notably, the VHTs should be trained and capable of dealing with COVID-19 related Psychosocial symptoms in the community. This idea is supported by studies conducted elsewhere in Africa, which suggest a grass-root approach to mental health problems after African countries’ lockdown [12,19].

The independent determinants of COVID-19 cases treated at Gulu Regional Referral Hospital

This study showed that the recovery rate from the COVID-19 treated at the Gulu Hospital was 95.2%, yet 99.5% of the COVID-19 patients were unvaccinated (Table 3). Furthermore, this study found the Adjusted Odds Ratios (AOR) for factors associated with COVID-19 patients’ recovery at GRRH were treatment with steroids AOR=138.835 at 95% CI:12.258-1572.50;p<0.000 and Vitamin D AOR=0.016 at 95% CI:1.902-520.98;p=0.016 (Table 8). Statistically significant associations of Vitamin D and steroids with favourable treatment and management outcomes of COVID 19 patients in our study have also been observed in previous studies [20,21]. Could these successes be specific for this centre, or could this apply to diverse settings worldwide? A formal review study in different locations would be required in the long term to determine the effectiveness of the drugs in managing mild and severe cases of COVID-19. Authors recommend global studies on the two drugs to assess their effects on the treatment outcomes of COVID-19 patients.

Circumstances under which the coronavirus infected participants

Findings show that most of the circumstances were unknown 581(87.5%), others were congregated situations such overcrowding at Elegu border and interacting with international truck drivers 50(7.5%), Aswa dam construction workers 12(1.8%) who lived in dormitories, health facility 2(0.3%), persons who nursed a relative with COVID-19 2(0.3%), bars 1(0.2%) and others 16(2.4%). This finding implies that the known source of the COVID-19 infection in Northern Uganda was from contacts with international truck drivers and mainly at the Elegu border point. Other sources such as bars, churches, and markets were fewer. Authors argue that regional controls of COVID-19 would be ideal for the East African region, where there is brisk trade among the countries. Therefore, the management and surveillance of international truck drivers as a regional approach would be suitable for controlling the coronavirus, ensuring that COVID-19 testing and management are conducted as per the international protocols across all the East African countries [11].

This study was a retrospective review of datasets from the COVID-19 medical records of Gulu Regional Referral Hospital. The period of the evaluation was from March 2020 to October 2021. The study has limitations on how Gulu Hospital handled records and record keeping. In addition, vital information, for example, weight, height, and BMI of COVID-19 patients, was not recorded due to the emergency handling of the cases at the beginning of the pandemic in March 2020. The missing variables in the Gulu Hospital HMIS records excluded some files from participating in this study. In this, authors have suggested a need for a prospective or longitudinal assessment of the COVID-19 cases in the future, ensuring that all data were measured and recorded accordingly.

This data is vital as it is one of the well-documented completed data for over 664 cases of COVID-19 treated in a Regional Referral Hospital in Uganda. Findings from this study show tremendous and good clinical practices at Gulu Regional Referral Hospital despite the challenges faced during the pandemic.

These findings should be cautiously interpreted and generalized only to Regional Referral Hospitals in Uganda. However, they could be similarly observed in many hospitals in African countries with lowresource settings.

This study shows successful management of COVID-19 patients in low resource settings in Gulu Regional Referral Hospital with a recovery rate of 95.2%. The pattern of admission to the Hospital suggests Uganda has experienced three waves of COVID-19, contrary to the official government position of two waves. Treatment of COVID-19 patients with steroids and Vitamin D is associated with recovery of COVID 19 patients. However, there is a need for Randomized Controlled Trials to determine the actual effects of these drugs in the treatment of COVID-19 infections.

Ethics approval and consent to participate

The Gulu Regional Referral Hospital Institutional and Ethics Committee approved this study. In addition, the study was conducted following the relevant institutional guidelines and regulations.

All datasets supporting the conclusion in this article is within this article and is accessible by a reasonable request to the corresponding author.

All authors declare no conflict of interest.

Most funding for this study was contributions of individual research members of the Uganda Medical Association (UMA) Acholi branch.

DLK, ENI, PL, JNO, JA, and FWDO participated in designing the study, SB and DLK were responsible for data abstraction supervision, BS, JA, ENI, and DLK were responsible for data analysis, interpretation, writing, and CO, NAO, WAO, BT, JE, PA, PL, FPP, DA, JNO, FWDO, for revising the manuscript.

We acknowledge with many thanks to the support from the administration of Gulu Regional Referral Hospital for the information obtained. Dr. Laban Oketcho, Dr. Anek Janet Schola, Dr. Baguma Steven, and Mr. Dominic Ogwal Savio for the well-collected data from the archives of Gulu Regional Referral Hospital. We also thank Mr. Lawrence Obalim for the data analysis well conducted. In addition, financial support from UMA Acholi branch members, which enabled the team to conduct this study successfully, is most appreciated. In honour of our two fallen colleagues (Co-authors), Dr. Paska Layet and Dr. Oola Janet, may their souls rest in peace!